The antivascular action of physiotherapy ultrasound on a murine tumor: role of a microbubble contrast agent.

This study investigated whether a microbubble-containing ultrasound contrast agent had a role in the antivascular action of physiotherapy ultrasound on tumor neovasculature. Ultrasound images (B-mode and contrast-enhanced power Doppler [0.02 mL Definity]) were made of 22 murine melanomas (K1735(22)). The tumor was insonated (I(SATA) = 1.7 W cm(-2), 1 MHz, continuous output) for 3 min and the power Doppler observations of the pre- and postinsonation tumor vascularities were analyzed. Significant reductions (p = 0.005 for analyses of color-weighted fractional area) in vascularity occurred when a contrast-enhanced power Doppler study occurred before insonation. Vascularity was unchanged in tumors without a pretherapy Doppler study. Histologic studies revealed tissue structural changes that correlated with the ultrasound findings. The underlying etiology of the interaction between the physiotherapy ultrasound beam, the microbubble-containing contrast agent and the tumor neovasculature is unknown. It was concluded that contrast agents play an important role in the antivascular effects induced by physiotherapy ultrasound.

[1]  O. Altland,et al.  Low‐intensity ultrasound increases endothelial cell nitric oxide synthase activity and nitric oxide synthesis , 2004, Journal of thrombosis and haemostasis : JTH.

[2]  Juan Tu,et al.  Intravascular inertial cavitation activity detection and quantification in vivo with Optison. , 2006, Ultrasound in medicine & biology.

[3]  R. Jain.  Tumor angiogenesis and accessibility: role of vascular endothelial growth factor. , 2002, Seminars in oncology.

[4]  E Stride,et al.  The potential for thermal damage posed by microbubble ultrasound contrast agents. , 2004, Ultrasonics.

[5]  J. Bai,et al.  A microbubble agent improves the therapeutic efficiency of high intensity focused ultrasound: a rabbit kidney study , 2004, Urological Research.

[6]  E. Conant,et al.  Quantitative vascularity of breast masses by Doppler imaging: regional variations and diagnostic implications. , 2000, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[7]  C. Sehgal,et al.  Histopathological observations of the antivascular effects of physiotherapy ultrasound on a murine neoplasm. , 2006, Ultrasound in medicine & biology.

[8]  Wen-zhi Chen,et al.  Pathological changes in human malignant carcinoma treated with high-intensity focused ultrasound. , 2001, Ultrasound in medicine & biology.

[9]  Kullervo Hynynen,et al.  Microbubble contrast agent with focused ultrasound to create brain lesions at low power levels: MR imaging and histologic study in rabbits. , 2006, Radiology.

[10]  Joshua D. Hutcheson,et al.  Quantification of optison bubble size and lifetime during sonication dominant role of secondary cavitation bubbles causing acoustic bioeffects. , 2004, The Journal of the Acoustical Society of America.

[11]  C. Sehgal,et al.  Renal blood flow changes induced with endothelin-1 and fenoldopam mesylate at quantitative Doppler US: initial results in a canine study. , 2001, Radiology.

[12]  E. Carstensen,et al.  Remnants of Albunex nucleate acoustic cavitation. , 1997, Ultrasound in medicine & biology.

[13]  P. Carmeliet,et al.  Angiogenesis in cancer and other diseases , 2000, Nature.

[14]  A. Brayman,et al.  Correlation between inertial cavitation dose and endothelial cell damage in vivo. , 2006, Ultrasound in medicine & biology.

[15]  D. Razansky,et al.  Enhanced heat deposition using ultrasound contrast agent - modeling and experimental observations , 2006, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[16]  Wen-zhi Chen,et al.  Tumor vessel destruction resulting from high-intensity focused ultrasound in patients with solid malignancies. , 2002, Ultrasound in medicine & biology.

[17]  Peter Carmeliet,et al.  Growing better blood vessels , 2001, Nature Biotechnology.

[18]  B. Teicher.  Antiangiogenic agents in cancer therapy , 1998 .

[19]  M. Dewhirst,et al.  Angiogenesis and Oxygen Transport in Solid Tumors , 1999 .

[20]  Shan-hui Hsu,et al.  Bioeffect of ultrasound on endothelial cells in vitro. , 2004, Biomolecular engineering.

[21]  Michael D Feldman,et al.  The antivascular action of physiotherapy ultrasound on murine tumors. , 2005, Ultrasound in medicine & biology.

[22]  C. Cain,et al.  Microbubble-enhanced cavitation for noninvasive ultrasound surgery , 2003, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[23]  Morton W. Miller,et al.  Acoustic cavitation nuclei survive the apparent ultrasonic destruction of Albunex microspheres. , 1997, Ultrasound in medicine & biology.